Annals of Gastroenterology (2013) 26, 212-219
REVIEW
Serrated polyps of right colon: guilty or innocent? George Michalopoulos, Charalampos Tzathas Tzaneion General Hospital, Piraeus, Greece
Abstract
In recent years a lot of interest has been focused on a specific category of polyps, the so-called serrated polyps which until recently were categorized with the hyperplastic or mixed polyps and were thought to have no risk of malignant transformation. Recently though, the serrated pathway of carcinogenesis was discovered and destroyed this myth. It is believed that up to one third of all colorectal cancers arise through the serrated pathway; these cancers occur more often in the proximal colon and have specific molecular characteristics. Specific subtypes of serrated polyps (mainly the sessile serrated adenomas/polyps) are thought to be precursor lesions of these cancers. The prevention of these cancers is a challenge for gastroenterologists because their location and endoscopic characteristics renders them difficult to detect. Also, although there is a clear need for creating a specific post-polypectomy surveillance program for these lesions, to date there have been no guidelines for surveillance with a high level of evidence. In this article the main molecular, endoscopic, histological and epidemiologic characteristics of these lesions are presented, as well as recommendations for surveillance. Keywords Serrated polyps, sessile serrated polyps, traditional serrated adenoma, colorectal cancer, surveillance
Ann Gastroenterol 2013; 26 (3): 212-219
Introduction The term serrated polyps was used for the first time in 1990 by Longacre and Fenoglio- Preiser and until recently this category of polyps was included in a larger group that was called “hyperplastic” or “mixed hyperplastic/adenomatous” polyps [1]. At the same time it was believed that these polyps had no potential for malignant transformation and for that reason they did not require polypectomy or surveillance. However, in recent years, after the discovery of the “serrated pathway” of carcinogenesis, specific groups of these polyps have been incriminated as precursor lesions of colorectal cancer (CRC).
Molecular features of the serrated pathway of carcinogenesis There are at least three basic molecular pathways of CRC development: 1) the pathway of chromosomal instability (CIN) which is responsible for 70-85% of CRCs [2] and is associated Gastroenterology Department, Tzaneion General Hospital, Piraeus, Greece Conflict of Interest: None Correspondence to: George Michalopoulos, Gastroenterology Department, Tzaneion General Hospital, Piraeus, Greece, Zani and Afentouli 1, 18536 Piraeus, Greece, Tel.: +30 210 4592896, Fax: +30 210 4592897, e-mail:
[email protected] Received 12 March 2013; accepted 9 April 2013 © 2013 Hellenic Society of Gastroenterology
with conventional adenomas; in this pathway there are common mutations of the APC (adenomatous polyposis coli) gene as well as mutations at the KRAS oncogene and β-catenin (CTNNB1) [3,4]; 2) the pathway of CpG (Cytosine Guanine phosphodiester bond) island methylator phenotype (CIMP) which is the second main pathway of sporadic CRC development and includes sporadic CRCs with high microsatellite instability (MSI-H); in this pathway common mutations of the BRAF gene are observed and in a smaller percentage of the KRAS oncogene [3]; and 3) the pure MSI pathway which is caused by mutations in the mismatch repair gene (MMR). The hereditary non-polyposis colorectal cancer (HNPCC) syndrome occurs through the pure MSI pathway [3]. The serrated pathway of carcinogenesis is actually the pathway of the CIMP [3].
Classification of serrated polyps In 2010 the World Health Organization (WHO) published a classification for serrated polyps (Table 1) [5]. The subtypes of these serrated lesions have different molecular features (mutations) and also different potential for malignant transformation to CRC. Hyperplastic polyps (HP) are very common, of small size (
